Department of Chemical and Biological Engineering, Tufts University, Medford, Massachusetts 02155, USA; email:
Artie McFerrin Department of Chemical Engineering and Department of Biomedical Engineering, Texas A&M University, College Station, Texas 77843, USA; email:
Annu Rev Biomed Eng. 2021 Jul 13;23:339-357. doi: 10.1146/annurev-bioeng-010220-095711. Epub 2021 Apr 14.
The rise of antibiotic-resistant strains of bacterial pathogens has necessitated the development of new therapeutics. Antimicrobial peptides (AMPs) are a class of compounds with potentially attractive therapeutic properties, including the ability to target specific groups of bacteria. In nature, AMPs exhibit remarkable structural and functional diversity, which may be further enhanced through genetic engineering, high-throughput screening, and chemical modification strategies. In this review, we discuss the molecular mechanisms underlying AMP selectivity and highlight recent computational and experimental efforts to design selectively targeting AMPs. While there has been an extensive effort to find broadly active and highly potent AMPs, it remains challenging to design targeting peptides to discriminate between different bacteria on the basis of physicochemical properties. We also review approaches for measuring AMP activity, point out the challenges faced in assaying for selectivity, and discuss the potential for increasing AMP diversity through chemical modifications.
抗生素耐药性细菌病原体的出现使得新疗法的开发成为必要。抗菌肽（AMPs）是一类具有潜在吸引力的治疗特性的化合物，包括靶向特定细菌群体的能力。在自然界中，AMPs 表现出显著的结构和功能多样性，通过基因工程、高通量筛选和化学修饰策略可以进一步增强这种多样性。在这篇综述中，我们讨论了 AMP 选择性的分子机制，并强调了最近为设计具有选择性靶向能力的 AMP 而进行的计算和实验努力。虽然已经进行了广泛的努力来寻找广泛有效的高活性 AMP，但设计针对基于物理化学性质区分不同细菌的靶向肽仍然具有挑战性。我们还回顾了测量 AMP 活性的方法，指出了在测定选择性方面面临的挑战，并讨论了通过化学修饰增加 AMP 多样性的潜力。
